Long-Term Cannabidiol Treatment Prevents the Development of Social Recognition Memory Deficits in Alzheimer's Disease Transgenic Mice
Long-Term Cannabidiol Treatment Prevents the Development of Social Recognition Memory Deficits in Alzheimer's Disease Transgenic Mice
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DOI：
10.3233/jad-140921
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Karl, Tim
中科院分区：
文献类型：
--
作者：
Cheng, David;Spiro, Adena S.;Karl, Tim
认知能力受损和由神经毒性、神经炎症、氧化损伤和胆固醇稳态改变引起的广泛病理生理变化与阿尔茨海默病（AD）相关。大麻二酚（CBD）已被证明可以逆转AD转基因小鼠的认知缺陷，并在体外和体内发挥神经保护，抗氧化和抗炎特性。在这里，我们评估了长期CBD治疗在雄性A β PPSwe/PS1 Delta E9（A β PP x PS1）小鼠（AD的转基因模型）中的预防特性。对照和AD转基因小鼠从2.5月龄开始每天口服CBD（20 mg/kg），持续8个月。然后，在分析皮质和海马组织的淀粉样蛋白负荷、氧化损伤、胆固醇、植物甾醇和炎症之前，在社会偏好测试、高架十字迷宫和恐惧条件化范例中评估小鼠。我们发现A β PP x PS1小鼠出现了社会识别缺陷，这是通过CBD治疗预防的。CBD对焦虑或联想学习没有影响。社会认知缺陷的预防与淀粉样蛋白负荷或氧化损伤的任何变化无关。然而，该研究揭示了CBD对神经炎症，胆固醇和膳食植物甾醇保留的微妙影响，值得进一步研究。这项研究首次证明了CBD能够预防AD转基因小鼠社会识别缺陷的发展。我们的研究结果提供了第一个证据，表明CBD可能具有作为AD预防性治疗的潜力，与社交退缩和面部识别症状特别相关。
Impairments in cognitive ability and widespread pathophysiological changes caused by neurotoxicity, neuroinflammation, oxidative damage, and altered cholesterol homeostasis are associated with Alzheimer's disease (AD). Cannabidiol (CBD) has been shown to reverse cognitive deficits of AD transgenic mice and to exert neuroprotective, anti-oxidative, and anti-inflammatory properties in vitro and in vivo. Here we evaluate the preventative properties of long-term CBD treatment in male A beta PPSwe/PS1 Delta E9 (A beta PP x PS1) mice, a transgenic model of AD. Control and AD transgenic mice were treated orally from 2.5 months of age with CBD (20 mg/kg) daily for 8 months. Mice were then assessed in the social preference test, elevated plus maze, and fear conditioning paradigms, before cortical and hippocampal tissues were analyzed for amyloid load, oxidative damage, cholesterol, phytosterols, and inflammation. We found that A beta PP x PS1 mice developed a social recognition deficit, which was prevented by CBD treatment. CBD had no impact on anxiety or associative learning. The prevention of the social recognition deficit was not associated with any changes in amyloid load or oxidative damage. However, the study revealed a subtle impact of CBD on neuroinflammation, cholesterol, and dietary phytosterol retention, which deserves further investigation. This study is the first to demonstrate CBD's ability to prevent the development of a social recognition deficit in AD transgenic mice. Our findings provide the first evidence that CBD may have potential as a preventative treatment for AD with a particular relevance for symptoms of social withdrawal and facial recognition.